ECT temporarily increases expression of certain inflammatory cytokine genes. However, multiple sessions of ECT leads to a decline in the levels of inflammatory mediators. ECT has been hypothesized to enhance release of hormones from hypothalamus into CSF and blood through excitation of diencephalic structures.
Evidences indicate disturbed levels of stress hormones in patients with mood disorder. In patients with depression, studies have consistently reported HPA axis hyper-function. This is evident in form of elevated cortisol levels and decreased cortisol suppression on dexamethasone suppression test.
High cortisol levels have negative impact on neurogenesis, gliogenesis and are related to atrophy of structures such as hippocampus. It is considered as a crucial site of glial-neuronal interaction and dysfunctions there might result in neuropsychiatric manifestations.
Whether these changes in levels of hormones have therapeutic implications or are manifestations of ECS related stress and to secondary other changes in brain is still unclear. However, ECT has been demonstrated to reduce cortisol induced inhibition of neuroplasticity. Disturbed monoaminergic neurotransmission has been proposed since long in depressed patients. In MDD patients dopamine transporter binding is reduced in the substantia nigra, striatum, thalamus, and anterior cingulate.
ECT series has been shown to elevate levels of CSF homovanillic acid and 5-hydroxyindoleacetic acid, the metabolites of monoamine neurotransmitters. Serotonergic neurotransmitter system is well known to have implications in disorders of mood and psychosis. Various antidepressants targeting this system have been developed. Researchers reported both increased response as well as no change in 5-HT 1A receptor sensitivity.
Antidepressant medications are associated with initial decline in 5-HT 1A receptor down-regulation, before resetting of serotonergic system occurs in neurons. Moreover, a study using neuroendocrine challenge test in patients undergoing ECT, could not find association between illness improvement and serotonergic function. Robust evidences for the direct involvement of serotonergic system in ECT are lacking at this point of time.
Further research in this domain might throw light on implications of serotonergic system in ECT action. Neuropeptide Y NPY has roles in emotional regulation, processing of memory, maintaining circadian rhythms, and regulation of appetite. Moreover, it also has anticonvulsant action and gets released in response to seizure stimulation. This effect is achieved through inhibitory effect of NPY on glutamatergic neurons.
Diminished NPY levels have been reported in various psychiatric disorders such as depression with suicidality, bipolar disorder and schizophrenia. Glutamate is the most abundant excitatory neurotransmitter in human brain.
Excessive release of glutamate is associated with overstimulation of extrasynaptic NMDA receptors leading to calcium influx inside neurons subsequently causing excitotoxic neuronal damage. The cystine glutamate antiporter located on astrocytes is involved in cystine uptake into cell in return for glutamate release.
Cystine gets reduced to cysteine, a substrate for the synthesis of glutathione which has antioxidant properties. Extracellular glutamate excess competitively prevents cystine uptake inside cell, triggering oxidative stress related cellular death.
In MDD patients, altered expression of glutamate receptors genes in hippocampus has also been reported. Dong et al. This glutamate normalizing action of ECT relates with improvement in disorders of mood.
In psychiatric disorders alterations in volume of brain structures has been consistently reported. Studies have also demonstrated ECT to trigger changes in volume of whole brain as well as its components such as gray matter, white matter and other brain structures. Neuroplastic changes have been noticed as early as after a single electroconvulsive stimulus. In rodents, ECS enhances markers of glial activation within hours of its application. This change was not associated with neuronal loss, ruling out it being just a compensatory activity.
Moreover, significant modulations in volume of brain substructures such as hippocampus, amygdala, anterior cingulate gyrus and medial and inferior temporal cortex have been reported with ECT. Furthermore, smaller baseline hippocampus volume had been suggested to be associated with greater post ECT clinical response. Additionally, FC changes were not found to correlate with hippocampal volume changes.
Several researches have also reported significant volume change in amygdala with ECT. Ota et al. Instead, Ten Doesschate et al. However, evidences regarding these associations are conflicting and require further exploration. Mounting evidences suggest alterations in connectivity within functional networks as well as between distinct networks, among patients with depression.
These networks are associated with top down regulation of attention and mood fronto-parietal network , processing of emotion the affective network and the ventral attention network as well as internally or externally oriented attention default mode [DM] network and dorsal attention network.
Studies have shown hyperconnectivity pattern in DM network in depression. Moreover, connectivity was decreased between the SgACC and left precuneus; thus, highlighting impairment in above mentioned networks. ECT normalizes resting state FC of brain networks. Furthermore, the elevation of connectivity was reported to correlate with symptom improvement in depression.
They suggested that FC changes occur initially in intra-limbic networks and subsequently extend to limbic-prefrontal networks.
Changes in resting state FC in several brain structures such as ACC, thalamus and hippocampus are associated both with ECT application as well as clinical improvement.
Decades of research performed to elucidate the mechanism of ECT outlined a vast field of study that may involve numerous intricate biologic processes, including alterations in neuroplasticity, levels of various neurotrophic factors and neurotransmitters, FC, immune mechanisms, neuroendocrine function as well as epigenetic processes. Despite the evidences explaining neurobiological mechanisms of ECT, inconsistent research findings preclude from drawing firm inferences.
This attributable to lacunae in present literature, such as lack of homogeneity in research methodology and study population, small to moderate sample size and lack of control group in numerous studies. Moreover, the cause-effect relationship between findings and therapeutic effects of ECT could not be established with absolute certainty and even it is also not very prudent to assume about a single mechanism that can explain the therapeutic effect of ECT.
The future researches focusing on neurobiologic mechanisms of ECT need to address following areas of concern; use of control groups, homogenous study methodology in a larger study population and to attend the grey areas where contrasting evidences exist.
National Center for Biotechnology Information , U. Journal List Clin Psychopharmacol Neurosci v. Clin Psychopharmacol Neurosci. Published online Aug Amit Singh and Sujita Kumar Kar.
Author information Article notes Copyright and License information Disclaimer. P, India. This article has been cited by other articles in PMC. Abstract Electroconvulsive therapy ECT is a time tested treatment modality for the management of various psychiatric disorders.
Keywords: Electroconvulsive therapy, Neurobiology, Psychiatric diagnosis. Neurophysiological Hypotheses The electrical impulse from ECT electrodes traverses through intermediary tissue to stimulate neurons in brain by altering their internal electrical milieu and concentration of ions.
Changes in blood brain barrier During the ictal phase of ECT induced seizure, there occurs an up-surge in blood pressure, consequently, there may occur break in the continuity of blood brain barrier BBB transiently. Electroencephalography changes Electroencephalography EEG reflects the functional integrity of the cerebral cortex.
Neurobiochemical Hypotheses ECT modulates the process of neurotransmission and influences the expression as well as release of a great variety of neurochemicals in brain including transcription factors, neurotransmitters, neurotrophic factors, and hormones. Neurotrophic factors There is increasing evidence for role of neurotrophic factors in growth and development of brain structures as well as in pathophysiology and treatment of psychiatric disorders.
Immune system Ongoing researches hinted towards a possible involvement of immune system in mediating the effects of ECT. Hormones Hypothalamic-pituitary-adrenal HPA axis ECT has been hypothesized to enhance release of hormones from hypothalamus into CSF and blood through excitation of diencephalic structures.
Mono-aminergic neurotransmitters Disturbed monoaminergic neurotransmission has been proposed since long in depressed patients. Serotonin Serotonergic neurotransmitter system is well known to have implications in disorders of mood and psychosis. Neuropeptide Y Neuropeptide Y NPY has roles in emotional regulation, processing of memory, maintaining circadian rhythms, and regulation of appetite. Glutamate Glutamate is the most abundant excitatory neurotransmitter in human brain.
Neuroplastic Changes In psychiatric disorders alterations in volume of brain structures has been consistently reported. Preanesthesia medical evaluation for electroconvulsive therapy: a review of the literature. J ECT. Pivotal role of tissue plasminogen activator in the mechanism of action of electroconvulsive therapy.
J Psychopharmacol. The mood-stabilizing effects of electroconvulsive therapy. Swartz CM. A mechanism of seizure induction by electricity and its clinical implications. Differences in cerebral blood flow between missed and generalized seizures with electroconvulsive therapy: a positron emission tomographic study.
Epilepsy Res. Controlling stimulation strength and focality in electroconvulsive therapy via current amplitude and electrode size and spacing: comparison with magnetic seizure therapy. Imaging onset and propagation of ECT-induced seizures. Burst suppression: a more valid marker of postictal central inhibition?
Changes in regional cerebral blood flow during acute electroconvulsive therapy in patients with depression: positron emission tomographic study. Br J Psychiatry. Resting hyperperfusion of the hippocampus, midbrain, and basal ganglia in people at high risk for psychosis. Am J Psychiatry. Abnormal grey matter arteriolar cerebral blood volume in schizophrenia measured with 3D inflow-based vascular-space-occupancy MRI at 7T. Schizophr Bull. A long-term follow-up of clinical response and regional cerebral blood flow changes in depressed patients treated with ECT.
J Affect Disord. Brain glucose metabolism difference between bipolar and unipolar mood disorders in depressed and euthymic states. Prog Neuropsychopharmacol Biol Psychiatry. Corticolimbic balance shift of regional glucose metabolism in depressed patients treated with ECT.
Decreased regional brain metabolism after ect. A preliminary study of the effects of electroconvulsive therapy on regional brain glucose metabolism in patients with major depression. Increased cerebral blood flow in depressed patients responding to electroconvulsive therapy. J Nucl Med. Share on: Facebook Twitter. Show references What is electroconvulsive therapy ECT?
American Psychiatric Association. Accessed Aug. National Alliance on Mental Illness. Brain stimulation therapies. National Institute of Mental Health. Kellner C. Overview of electroconvulsive therapy ECT for adults.
Technique for performing electroconvulsive therapy ECT in adults. Electroconvulsive therapy ECT. Rochester, Minn. Guidance on the use of electroconvulsive therapy. National Institute for Health and Care Excellence. Kolar D. Current status of electroconvulsive therapy for mood disorders: A clinical review. Evidence-Based Mental Health. Weiner RD, et al. Key updates in the clinical application of electroconvulsive therapy.
International Review of Psychiatry. Rasmussen KG, et al. An open-label, pilot study of daily right unilateral ultrabrief pulse electroconvulsive therapy. Journal of ECT. Acharya D, et al. Because patients are under anesthesia and have taken muscle relaxants, they neither convulse nor feel the current. Patients awaken about 5 to 10 minutes after the end of the treatment. Patients are then moved to the recovery room and remain there until their blood pressure, pulse and breathing return to their pre-treatment levels.
Usually this takes about 20 to 25 minutes. Patients who are given ECT on an outpatient basis must have someone drive them home after the procedure and stay with them until they go to sleep at night. People should not drive in the 24 hours following ECT.
A single ECT session usually lasts one hour. This includes the time the patient will be in the treatment room approximately minutes and the time spent in the recovery room approximately minutes. Typically, ECT whether inpatient or outpatient is given two to three times a week for a total of six to twelve sessions.
Some patients may need more or fewer treatments. These sessions improve depression in 70 to 90 percent of patients, a response rate much higher than that of antidepressant drugs. Although ECT is effective, its benefits are short-lived.
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